1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/18086388.csml convertedTime:2009.07.01.11:12

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Molecular mechanisms of the anti-inflammatory functions of interferons.
Authors Kovarik P, Sauer I, Schaljo B.
Affiliation Max F Perutz Laboratories, University of Vienna, Dr Bohr-Gasse 9, A-1030,Vienna, Austria. pavel.kovarik@univie.ac.at
Abstract Interferons are pleiotropic cytokines with important proinflammatory functionsrequired in defence against infections with bacteria, viruses and multicellularparasites. In recent years, fundamental functions of interferons in otherprocesses such as cancer immunosurveillance, immune homeostasis andimmunosuppression have been established. In addition, anti-inflammatory roles ofinterferons are well-documented in several inflammatory disease models in themouse, most importantly in experimental autoimmune encephalomyelitis thatresembles multiple sclerosis in humans. While the beneficial effects ofinterferons in such disease models are known, the molecular mechanisms remainpoorly understood. Only recently a few molecular principles for theanti-inflammatory properties of interferons at the cellular level have beenrevealed. They include the ability of interferons to reduce the expression ofthe receptors for the inflammation-related cytokines IL-1 and IL-4, or toincrease the expression of the potent anti-inflammatory genes tristetraprolinand Twist. However, the individual contribution of these anti-inflammatoryresponses to the overall beneficial effects of interferons in inflammatorydiseases is still an open question. Also, the reason for the apparently limitednumber of tissues that are susceptible to the anti-inflammatory functions ofinterferons remains enigmatic. This review summarizes the present knowledge ofthe anti-inflammatory effects of interferons, and describes the currently knownmolecular mechanisms that may help explain the benefits of interferon signallingin several inflammatory diseases.
PMID 18086388
Model Abstract

Entity

e1: e10: e11:type I IFN e12:type I IFN:IFNAR1:JAK1:IFNAR2:TYK2 e13:type I IFN:IFNAR1:JAK1{active}:IFNAR2:TYK2{active} e14:stat1{p}:stat2 e15:stat1{p} e16:stat1 e17:Stat2 e18:stat1{p}:stat2 e19:ISRE elements e2: e20:ISGF3:ISRE e21:IRF9 e22:ISGF3 complex e23:IFN-gamma e24:IFNGR1:JAK1 e25:IFNGR2:JAK2 e26:IFNGR1:JAK1:IFNGR2:JAK2:IFN-gamma e27:IFNGR1:JAK1{active}:IFNGR2:JAK2{active}:IFN-gamma e28:IFNGR1{p}:JAK1{active}:IFNGR2{p}:JAK2{active}:IFN-gamma e29:IFNGR1{p}:JAK1{active}:IFNGR2{p}:JAK2{active}:IFN-gamma:stat1 e3: e30:IFNGR1{p}:JAK1{active}:IFNGR2{p}:JAK2{active}:IFN-gamma:stat1{p} e31:(stat1{p})2 e32:(stat1{p})2 e33:GAS e34:GAS:(stat1{p})2 e35:IL-1R e36:Twist e37:Twist:TNF-alpha e38:E-box on TNF-alpha e39:IL-4R e4: e40:IFN-alpha e41:Twist e42:Twist e43:Axl e44:Axl e45:LPS e46:NF-kappaB e47:NF-kappaB{active} e48:Ig complex e49:TNF-alpha e5:IFNAR1:JAK1 e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:IFNAR2:TYK2 e60: e61: e62: e63:stat3{active} e64:stat3 e65:PERK e66:TTP e67:TTP:stat1 e68:(stat1{p})2{active} e69:p38MAPK e7: e70:TTP e71:TTP e72:TNF-alpha e73:PERK{active} e74:eIF2alpha{p} e75:eIF2alpha e8: e9:

Process

p1 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p2 p20 p21 p22 p23 p24 p25 p26 p27 p28 p29 p3 p30 p31 p32 p33 p34 p35 p36 p37 p4 p5 p6 p7 p8 p9
Model Detail
324.5080977697241, 125.0665133489266
1213.7568799704975, 1762.3749897171615

--

e1

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane

--

--

--

true true true true

csml-variable:Double

m1

0

false

infinite

0

unit false true false

--

Go back
336.20256079712556, 152.0035990087663
1176.5021011894066, 1655.0076421361368

--

e10

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytosol

--

--

--

true true true true

csml-variable:Double

m10

0

false

infinite

0

unit false true false

--

Go back
1691.0, 264.70386643233735
33.53251318101933, 21.796133567662565

type I IFN

--

e11

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p1

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
1484.0, 336.0000000000001
24.0, 40.00000000000001

type I IFN:IFNAR1:JAK1:IFNAR2:TYK2

--

e12

cso30:c:Complex

cso30:i:CC_Cytosol

--

p1

p2

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
1485.0, 429.97058823529414
21.61764705882353, 36.029411764705884

type I IFN:IFNAR1:JAK1{active}:IFNAR2:TYK2{active}

--

e13

cso30:c:Complex

cso30:i:CC_Cytosol

--

p2

p3 p22 p27

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
1246.0, 608.6132596685082
27.348066298342548, 30.386740331491712

stat1{p}:stat2

--

e14

cso30:c:Complex

cso30:i:CC_Cytosol

--

p4

p5

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
1343.0, 518.2926829268292
34.63414634146341, 27.70731707317073

stat1{p}

--

e15

cso30:c:Protein

cso30:i:CC_Cytosol

--

p3 p13

p4 p14

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
1150.0, 436.82642382773184
36.7679613604347, 22.67357617226806

stat1

--

e16

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p3 p11

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
1149.0, 520.66
29.119999999999997, 21.839999999999996

Stat2

--

e17

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p4

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
1070.0, 1260.6132596685084
27.348066298342548, 30.386740331491712

stat1{p}:stat2

--

e18

cso30:c:Complex

cso30:i:CC_Cytosol

--

p5

p6

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
861.0, 1229.9210665959142
53.441231095781376, 11.578933404085964

ISRE elements

--

e19

cso30:c:Dna

cso30:i:CC_Nucleoplasm

--

--

p7

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
324.5080977697241, 125.0665133489266
1213.7568799704975, 1762.3749897171615

--

e2

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m2

0

false

infinite

0

unit false true false

--

Go back
1038.0, 1299.5
60.0, 17.0

ISGF3:ISRE

--

e20

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

p7

--

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
922.0, 1189.3178707989534
35.971020326021325, 22.182129201046486

IRF9

--

e21

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p6

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
1005.5, 1256.311800330336
21.993209763259312, 30.68819966966416

ISGF3 complex

--

e22

cso30:c:Complex

cso30:i:CC_Cytosol

--

p6

p7

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
1056.0, 29.160808435852402
32.82952548330405, 21.339191564147633

IFN-gamma

--

e23

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p8 p34

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
879.5, 152.35510748208628
25.02666222296284, 30.64489251791368

IFNGR1:JAK1

--

e24

cso30:c:Complex

cso30:i:CC_Cytosol

--

--

p8

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
967.5, 153.12497917013843
24.397933677720374, 29.87502082986169

IFNGR2:JAK2

--

e25

cso30:c:Complex

cso30:i:CC_Cytosol

--

--

p8

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
1052.0, 143.85294117647055
24.08823529411765, 40.14705882352942

IFNGR1:JAK1:IFNGR2:JAK2:IFN-gamma

--

e26

cso30:c:Complex

cso30:i:CC_Cytosol

--

p8

p9 p17 p19

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
1137.0, 146.85294117647055
21.08823529411765, 35.14705882352941

IFNGR1:JAK1{active}:IFNGR2:JAK2{active}:IFN-gamma

--

e27

cso30:c:Complex

cso30:i:CC_Cytosol

--

p9

p10

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
1232.0, 143.3823529411764
24.970588235294116, 41.61764705882353

IFNGR1{p}:JAK1{active}:IFNGR2{p}:JAK2{active}:IFN-gamma

--

e28

cso30:c:Complex

cso30:i:CC_Cytosol

--

p10 p13

p11

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
1319.0, 150.64705882352945
25.411764705882355, 42.35294117647059

IFNGR1{p}:JAK1{active}:IFNGR2{p}:JAK2{active}:IFN-gamma:stat1

--

e29

cso30:c:Complex

cso30:i:CC_Cytosol

--

p11

p12

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
348.7832353691339, 149.34165094833668
1165.206604771677, 1713.8247145183418

--

e3

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m3

0

false

infinite

0

unit false true false

--

Go back
1393.0, 145.20588235294116
22.676470588235286, 37.79411764705882

IFNGR1{p}:JAK1{active}:IFNGR2{p}:JAK2{active}:IFN-gamma:stat1{p}

--

e30

cso30:c:Complex

cso30:i:CC_Cytosol

--

p12

p13

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
1348.5, 737.5747375437427
23.213964339276785, 28.42526245625729

(stat1{p})2

--

e31

cso30:c:Complex

cso30:i:CC_Cytosol

--

p14

p15

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
1152.5, 1321.5747375437427
23.213964339276785, 28.42526245625729

(stat1{p})2

--

e32

cso30:c:Complex

cso30:i:CC_Cytosol

--

p15

p16 p29

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
1030.0, 1361.5
60.0, 13.0

GAS

--

e33

cso30:c:Dna

cso30:i:CC_Cytosol

--

--

p16

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
1158.0, 1407.5
60.0, 17.0

GAS:(stat1{p})2

--

e34

cso30:c:Complex

cso30:i:CC_Cytosol

--

p16

p28

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
747.0, 1274.536332179931
34.61937716262976, 18.463667820069205

IL-1R

--

e35

cso30:c:mRNA

cso30:i:CC_Cytosol

--

p17

--

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
662.5, 1313.4528074059167
18.22076876635138, 29.547192594083313

Twist

--

e36

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p18 p25

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
770.0, 1383.5
60.0, 17.0

Twist:TNF-alpha

--

e37

cso30:c:Complex

cso30:i:CC_NuclearChromosome

--

p18

--

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
762.0, 1325.5
60.0, 13.0

E-box on TNF-alpha

--

e38

cso30:c:Dna

cso30:i:CC_Nucleoplasm

--

--

p18

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
818.0, 1578.6782006920416
36.22837370242215, 19.32179930795848

IL-4R

--

e39

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p19

--

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
393.69223992804257, 191.8231417473038
1075.3885956538609, 1628.861732920407

--

e4

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m4

0

false

infinite

0

unit false true false

--

Go back
693.0, 1911.2539543057997
38.84007029876977, 25.24604569420035

IFN-alpha

--

e40

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p19 p26 p35

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false false false

--

Go back
943.0, 1503.2006920415226
33.373702422145335, 17.79930795847751

Twist

--

e41

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p20

p21

true true true true

csml-variable:Double

m41

0

false

infinite

0

unit false false false

--

Go back
1385.5, 1494.9971825316964
20.968404105453814, 34.00281746830349

Twist

--

e42

cso30:c:Protein

cso30:i:CC_Cytosol

--

p21

--

true true true true

csml-variable:Double

m42

0

false

infinite

0

unit false false false

--

Go back
1093.0, 1547.5570934256054
45.83044982698962, 24.442906574394463

Axl

--

e43

cso30:c:mRNA

cso30:i:CC_Cytosol

--

p22

p27

true true true true

csml-variable:Double

m43

0

false

infinite

0

unit false false false

--

Go back
1040.0, 892.1399999999999
32.48, 24.359999999999996

Axl

--

e44

cso30:c:Protein

cso30:i:CC_Cytosol

--

p27

p20 p21

true true true true

csml-variable:Double

m44

0

false

infinite

0

unit false false false

--

Go back
189.0, 443.30698065601337
45.340622371740956, 25.693019343986542

LPS

--

e45

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p23

true true true true

csml-variable:Double

m45

0

false

infinite

0

unit false false false

--

Go back
508.0, 808.9176800748363
16.5023386342376, 38.082319925163695

NF-kappaB

--

e46

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p23 p24

true true true true

csml-variable:Double

m46

0

false

infinite

0

unit false false false

--

Go back
819.0, 758.8381665107578
18.703461178671652, 43.161833489242284

NF-kappaB{active}

--

e47

cso30:c:Protein

cso30:i:CC_Cytosol

--

p23 p24

p25

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false false false

--

Go back
312.5, 757.286121464591
23.102170576627927, 44.71387853540891

Ig complex

--

e48

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p24

true true true true

csml-variable:Double

m48

0

false

infinite

0

unit false false false

--

Go back
839.0, 1527.3391003460208
33.11418685121107, 17.660899653979243

TNF-alpha

--

e49

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p25

p33

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false false false

--

Go back
1479.5, 224.0951508081988
25.238960173304445, 30.904849191801357

IFNAR1:JAK1

--

e5

cso30:c:Complex

cso30:i:CC_Cytosol

--

--

p1

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
581.4319067050534, 1141.4260466604062
660.0639440875815, 598.6054762954423

--

e50

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelopeLumen

--

--

--

true true true true

csml-variable:Double

m50

0

false

infinite

0

unit false true false

--

Go back
652.7237293439357, 1155.6121262131273
385.95917773463816, 580.1679359577997

--

e51

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearPore

--

--

--

true true true true

csml-variable:Double

m51

0

false

infinite

0

unit false true false

--

Go back
590.0360921959532, 1149.4156474733845
642.8555731057828, 582.6262746694858

--

e52

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearInnerMembrane

--

--

--

true true true true

csml-variable:Double

m52

0

false

infinite

0

unit false true false

--

Go back
591.2652615517957, 1150.6448168292272
640.397234394097, 580.1679359577997

--

e53

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearLumen

--

--

--

true true true true

csml-variable:Double

m53

0

false

infinite

0

unit false true false

--

Go back
581.4319067050534, 1141.4260466604062
660.0639440875815, 598.6054762954423

--

e54

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearOuterMembrane

--

--

--

true true true true

csml-variable:Double

m54

0

false

infinite

0

unit false true false

--

Go back
581.4319067050534, 1141.4260466604062
660.0639440875815, 598.6054762954423

--

e55

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleus

--

--

--

true true true true

csml-variable:Double

m55

0

false

infinite

0

unit false true false

--

Go back
591.2652615517957, 1150.6448168292272
640.397234394097, 580.1679359577997

--

e56

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleoplasm

--

--

--

true true true true

csml-variable:Double

m56

0

false

infinite

0

unit false true false

--

Go back
1063.2662941954286, 1387.2599178289659
41.237168502562284, 37.33048938126697

--

e57

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearBody

--

--

--

true true true true

csml-variable:Double

m57

0

false

infinite

0

unit false true false

--

Go back
955.0993908812641, 1559.343627646957
116.7710888050656, 105.70856460248059

--

e58

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleolus

--

--

--

true true true true

csml-variable:Double

m58

0

false

infinite

0

unit false true false

--

Go back
581.4319067050534, 1141.4260466604062
660.0639440875815, 598.6054762954423

--

e59

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelope

--

--

--

true true true true

csml-variable:Double

m59

0

false

infinite

0

unit false true false

--

Go back
1484.5, 285.79470088318624
23.03432761206465, 28.20529911681386

IFNAR2:TYK2

--

e6

cso30:c:Complex

cso30:i:CC_Cytosol

--

--

p1

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
737.0052644023181, 1407.441374008331
20.903255247165927, 10.064530304191019

--

e60

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Chromatin

--

--

--

true true true true

csml-variable:Double

m60

0

false

infinite

0

unit false true false

--

Go back
736.3072455412457, 1377.4265629822246
71.54693325990613, 128.78447986783107

--

e61

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearChromosome

--

--

--

true true true true

csml-variable:Double

m61

0

false

infinite

0

unit false true false

--

Go back
766.3220565673528, 1461.1888263108947
11.168301777156062, 11.168301777156074

--

e62

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearCentromere

--

--

--

true true true true

csml-variable:Double

m62

0

false

infinite

0

unit false true false

--

Go back
532.0, 1480.26
32.32, 24.24

stat3{active}

--

e63

cso30:c:Protein

cso30:i:CC_Cytosol

--

p26

p28

true true true true

csml-variable:Double

m63

0

false

infinite

0

unit false false false

--

Go back
633.0, 1708.82
30.24, 22.68

stat3

--

e64

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p26

true true true true

csml-variable:Double

m64

0

false

infinite

0

unit false false false

--

Go back
853.0, 330.1347353592272
33.024753471523454, 20.365264640772793

PERK

--

e65

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p34

true true true true

csml-variable:Double

m65

0

false

infinite

0

unit false false false

--

Go back
1018.0, 1453.5
60.0, 13.0

TTP

--

e66

cso30:c:Dna

cso30:i:CC_Cytosol

--

--

p30 p35

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
890.0, 1403.5
60.0, 17.0

TTP:stat1

--

e67

cso30:c:Complex

cso30:i:CC_Cytosol

--

p30

p32

true true true true

csml-variable:Double

m67

0

false

infinite

0

unit false false false

--

Go back
988.5, 1325.4647558740207
23.303782702882852, 28.535244125979006

(stat1{p})2{active}

--

e68

cso30:c:Complex

cso30:i:CC_Cytosol

--

p29

p30

true true true true

csml-variable:Double

m68

0

false

infinite

0

unit false false false

--

Go back
759.0, 958.3723105706267
13.705332086061738, 31.627689429373245

p38MAPK

--

e69

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p29

true true true true

csml-variable:Double

m69

0

false

infinite

0

unit false false false

--

Go back
340.45509280708956, 132.15844962893408
1190.3173549086791, 1686.6489457008595

--

e7

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell

--

--

--

true true true true

csml-variable:Double

m7

0

false

infinite

0

unit false true false

--

Go back
892.0, 1645.961937716263
39.44636678200691, 21.03806228373702

TTP

--

e70

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p32 p35

p31

true true true true

csml-variable:Double

m70

0

false

infinite

0

unit false false false

--

Go back
1308.5, 1637.147514590461
22.72569933588247, 36.85248540953915

TTP

--

e71

cso30:c:Protein

cso30:i:CC_Cytosol

--

p31

p25 p33

true true true true

csml-variable:Double

m71

0

false

infinite

0

unit false false false

--

Go back
670.0, 1027.1
35.2, 26.400000000000002

TNF-alpha

--

e72

cso30:c:Protein

cso30:i:CC_Cytosol

--

p33

--

true true true true

csml-variable:Double

m72

0

false

infinite

0

unit false false false

--

Go back
855.0, 478.1347353592272
33.024753471523454, 20.365264640772793

PERK{active}

--

e73

cso30:c:Protein

cso30:i:CC_Cytosol

--

p34

p36

true true true true

csml-variable:Double

m73

0

false

infinite

0

unit false false false

--

Go back
798.0, 618.6341463414634
36.70731707317073, 29.365853658536583

eIF2alpha{p}

--

e74

cso30:c:Protein

cso30:i:CC_Cytosol

--

p36

p37

true true true true

csml-variable:Double

m74

0

false

infinite

0

unit false false false

--

Go back
678.0, 462.7839605554437
38.45844234252365, 23.716039444556248

eIF2alpha

--

e75

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p36

true true true true

csml-variable:Double

m75

0

false

infinite

0

unit false false false

--

Go back
344.7076248170537, 161.92617369868253
1141.885622112165, 1658.0179233068632

--

e8

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell_WithoutCellWall_

--

--

--

true true true true

csml-variable:Double

m8

0

false

infinite

0

unit false true false

--

Go back
356.0477101769579, 191.69389776843093
1136.6722878836854, 1636.2734337043935

--

e9

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

--

--

--

true true true true

csml-variable:Double

m9

0

false

infinite

0

unit false true false

--

Go back
1589.0, 265.0
21.0, 21.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e5 e6 e11

e12

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
stoichiometry:c3 : 1
stoichiometry:c4 : 1

m5*m6*m11*0.1

nodelay

--

true

0

false

PMID: 18086388, 15546383, 10526569 Binding of type I IFNs to their receptor (composed of the IFNAR1 and IFNAR2 subunits) activates the receptor-associated tyrosine kinases Jak1 and Tyk2 causing phosphorylation of the receptor and, subsequently, recruitment and phosphorylation of the Stat transcription factors

Go back
1198.0, 62.0
19.0, 19.0

p10

p10

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e27

e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c27 : 1
stoichiometry:c28 : 1

m27*0.1

nodelay

--

true

0

false

PMID: 18086388 The receptor-associated Jak1 and Jak2 tyrosine kinases are activated and phosphorylate the receptor, thereby generating a docking site for the SH2 domain of Stat1.

Go back
1290.0, 58.0
19.0, 19.0

p11

p11

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e28 e16

e29

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c29 : 1
stoichiometry:c30 : 1
stoichiometry:c31 : 1

m28*m16*0.1

nodelay

--

true

0

false

PMID: 18086388 The receptor-associated Jak1 and Jak2 tyrosine kinases are activated and phosphorylate the receptor, thereby generating a docking site for the SH2 domain of Stat1.

Go back
1382.0, 66.0
19.0, 19.0

p12

p12

cso30:i:ME_Phosphorylation

cso30:i:CC_Extracellular

--

e29

e30

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c32 : 1
stoichiometry:c33 : 1

m29*0.1

nodelay

--

true

0

false

PMID: 18086388 After phosphorylation by Jaks Stat1:Stat1 dimers translocate to the nucleus and activate transcription by binding to the GAS elements of IFN-¦Ã responsive genes.

Go back
1381.0, 237.0
21.0, 21.0

p13

p13

cso30:i:ME_Dissociation

cso30:i:CC_Cytosol

--

e30

e15 e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c34 : 1
stoichiometry:c35 : 1
stoichiometry:c36 : 1

m30*0.1

nodelay

--

true

0

false

PMID: 18086388 After phosphorylation by Jaks Stat1:Stat1 dimers translocate to the nucleus and activate transcription by binding to the GAS elements of IFN-¦Ã responsive genes.

Go back
1349.0, 629.0
21.0, 21.0

p14

p14

cso30:i:ME_Dimerization

cso30:i:CC_Cytosol

--

e15

e31

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c37 : 1
stoichiometry:c38 : 1

m15*0.1

nodelay

--

true

0

false

PMID: 18086388 After phosphorylation by Jaks Stat1:Stat1 dimers translocate to the nucleus and activate transcription by binding to the GAS elements of IFN-¦Ã responsive genes.

Go back
1326.0, 938.0
19.0, 19.0

p15

p15

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

e31

e32

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c39 : 1
stoichiometry:c40 : 1

m31*0.1

nodelay

--

true

0

false

PMID: 18086388 After phosphorylation by Jaks Stat1:Stat1 dimers translocate to the nucleus and activate transcription by binding to the GAS elements of IFN-¦Ã responsive genes.

Go back
1091.0, 1407.0
17.0, 17.0

p16

p16

cso30:i:ME_DNABinding

cso30:i:CC_Nucleoplasm

--

e32 e33

e34

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c42 : 1
stoichiometry:c43 : 1

m32*m33*0.1

nodelay

--

true

0

false

PMID: 18086388 After phosphorylation by Jaks Stat1:Stat1 dimers translocate to the nucleus and activate transcription by binding to the GAS elements of IFN-¦Ã responsive genes.

Go back
754.0, 1206.0
19.0, 19.0

p17

p17

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e26

e35

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c45 : 1
stoichiometry:c44 : 1

1.0*0.1

nodelay

--

true

0

false

PMID: 18086388, 15972639 The work by Hu and colleagues shows that IFN-¦Ã suppresses the expression of the IL-1 receptor in macrophages making the cells refractory to IL-1

Go back
696.0, 1384.0
15.0, 15.0

p18

p18

cso30:i:ME_DNABinding

cso30:i:CC_Nucleoplasm

--

e38 e36

e37

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c46 : 1
stoichiometry:c48 : 1
stoichiometry:c47 : 1

m38*m36*0.1

nodelay

--

true

0

false

PMID: 18086388, 12553906 Twist proteins are transcriptional repressors that bind to the E-boxes in gene promoters, such as the TNF-¦Á promoter, and inhibit transcription

Go back
701.0, 1576.0
23.0, 23.0

p19

p19

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e40 e26

e39

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c50 : 1
stoichiometry:c51 : 1
stoichiometry:c49 : 1

1.0*0.1

nodelay

--

true

0

false

PMID: 18086388, 11067899 Both IFN-¦Á and IFN-¦Ã were found to decrease the IL-4 receptor gene expression

Go back
1578.0, 406.0
19.0, 19.0

p2

p2

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e12

e13

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c5 : 1
stoichiometry:c6 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18086388, 15546383, 10526569 Binding of type I IFNs to their receptor (composed of the IFNAR1 and IFNAR2 subunits) activates the receptor-associated tyrosine kinases Jak1 and Tyk2 causing phosphorylation of the receptor and, subsequently, recruitment and phosphorylation of the Stat transcription factors

Go back
949.0, 1373.0
21.0, 21.0

p20

p20

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e44

e41

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c52 : 1

m44*0.1

nodelay

--

true

0

false

PMID: 18086388 type I IFNs increase the amount of Twist proteins in cells and, consequently, the pre-treatment of macrophages with type I IFNs reduces the capability of immunoglobulin complexes or LPS to stimulate the NF-¦ÊB-mediated expression of TNF-¦Á.

Go back
1274.0, 1502.0
19.0, 19.0

p21

p21

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e41 e44

e42

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c59 : 1
stoichiometry:c54 : 1

m41*m44*0.1

nodelay

--

true

0

false

PMID: 18086388 type I IFNs increase the amount of Twist proteins in cells and, consequently, the pre-treatment of macrophages with type I IFNs reduces the capability of immunoglobulin complexes or LPS to stimulate the NF-¦ÊB-mediated expression of TNF-¦Á.

Go back
1042.0, 1550.0
19.0, 19.0

p22

p22

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e13

e43

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c56 : 1
stoichiometry:c55 : 1

m13*0.1

nodelay

--

true

0

false

PMID: 18086388 The up-regulation of Twist by IFNs was indirect and required the IFN-induced expression of the receptor tyrosine kinase Axl.

Go back
689.0, 692.0
15.0, 15.0

p23

p23

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e45 e46

e47

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c60 : 1
stoichiometry:c61 : 1
stoichiometry:c62 : 1

m45*m46*0.1

nodelay

--

true

0

false

PMID: 18086388 type I IFNs increase the amount of Twist proteins in cells and, consequently, the pre-treatment of macrophages with type I IFNs reduces the capability of immunoglobulin complexes or LPS to stimulate the NF-¦ÊB-mediated expression of TNF-¦Á.

Go back
690.0, 818.0
19.0, 19.0

p24

p24

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e46 e48

e47

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c63 : 1
stoichiometry:c65 : 1
stoichiometry:c64 : 1

m46*m48*0.1

nodelay

--

true

0

false

PMID: 18086388 type I IFNs increase the amount of Twist proteins in cells and, consequently, the pre-treatment of macrophages with type I IFNs reduces the capability of immunoglobulin complexes or LPS to stimulate the NF-¦ÊB-mediated expression of TNF-¦Á.

Go back
866.0, 1438.0
19.0, 19.0

p25

p25

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e47 e36 e71

e49

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c70 : 1
stoichiometry:c68 : 1
stoichiometry:c86 : 1
stoichiometry:c69 : 1

m47*0.1

nodelay

--

true

0

false

PMID: 18086388 type I IFNs increase the amount of Twist proteins in cells and, consequently, the pre-treatment of macrophages with type I IFNs reduces the capability of immunoglobulin complexes or LPS to stimulate the NF-¦ÊB-mediated expression of TNF-¦Á. PMID: 18086388 TTP limits the production of TNF-¦Á under these conditions

Go back
541.0, 1646.0
13.0, 13.0

p26

p26

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e64 e40

e63

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c71 : 1
stoichiometry:c73 : 1
stoichiometry:c72 : 1

m64*m40*0.1

nodelay

--

true

0

false

PMID: 18086388, 16571725 In their paper, Ho and Ivashkiv show that IFN-¦Á-activated Stat3 inhibited, in a dose-dependent manner, the transcription of genes that are regulated by Stat1:Stat1 homodimers while the transcription of the ISGF3 (Stat1:Stat2:IRF9) target genes remained unaffected.

Go back
1305.0, 1392.0
23.0, 23.0

p27

p27

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e43 e13

e44

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c57 : 1
stoichiometry:c67 : 1
stoichiometry:c66 : 1

m43*m13*0.1

nodelay

--

true

0

false

PMID: 18086388 The up-regulation of Twist by IFNs was indirect and required the IFN-induced expression of the receptor tyrosine kinase Axl.

Go back
1129.0, 1480.0
23.0, 23.0

p28

p28

cso30:i:ME_Transcription

cso30:i:CC_Nucleoplasm

--

e63 e34

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c74 : 1
stoichiometry:c75 : 1

m34*0.1

nodelay

--

true

0

false

PMID: 18086388, 16571725 In their paper, Ho and Ivashkiv show that IFN-¦Á-activated Stat3 inhibited, in a dose-dependent manner, the transcription of genes that are regulated by Stat1:Stat1 homodimers while the transcription of the ISGF3 (Stat1:Stat2:IRF9) target genes remained unaffected.

Go back
1093.0, 1329.0
21.0, 21.0

p29

p29

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e32 e69

e68

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c76 : 1
stoichiometry:c81 : 1
stoichiometry:c77 : 1

m32*m69*0.1

nodelay

--

true

0

false

PMID: 18086388 Stat1 is recruited to the TTP promoter regardless of p38 MAPK activation, but it requires p38 MAPK to become transcriptionally active.

Go back
1327.0, 439.0
17.0, 17.0

p3

p3

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e16 e13

e15

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c9 : 1
stoichiometry:c8 : 1

m16*m13*0.1

nodelay

--

true

0

false

PMID: 18086388, 11226159, 12671680, 14670297, 7543024 For full responses to both type I and type II IFNs the transactivation domain of Stat1 needs to be phosphorylated on serine 727

Go back
992.0, 1399.5
16.5, 16.5

p30

p30

cso30:i:ME_DNABinding

cso30:i:CC_Cytosol

--

e66 e68

e67

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c78 : 1
stoichiometry:c80 : 1
stoichiometry:c79 : 1

m66*m68*0.1

nodelay

--

true

0

false

PMID: 18086388 Stat1 is recruited to the TTP promoter regardless of p38 MAPK activation, but it requires p38 MAPK to become transcriptionally active.

Go back
1225.0, 1646.0
17.0, 17.0

p31

p31

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e70

e71

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c85 : 1
stoichiometry:c84 : 1

m70*0.1

nodelay

--

true

0

false

PMID: 18086388 We have demonstrated that both types of IFNs can, in a Stat1-dependent way, induce TTP provided the stress-regulated p38 MAPK is activated simultaneously.

Go back
903.0, 1535.0
17.0, 17.0

p32

p32

cso30:i:ME_Transcription

cso30:i:CC_Nucleoplasm

--

e67

e70

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c82 : 1
stoichiometry:c83 : 1

m67*0.1

nodelay

--

true

0

false

PMID: 18086388 We have demonstrated that both types of IFNs can, in a Stat1-dependent way, induce TTP provided the stress-regulated p38 MAPK is activated simultaneously.

Go back
687.0, 1111.0
25.0, 25.0

p33

p33

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e49 e71

e72

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c88 : 1
stoichiometry:c89 : 1
stoichiometry:c87 : 1

m49*0.1

nodelay

--

true

0

false

PMID: 18086388 TTP limits the production of TNF-¦Á under these conditions

Go back
862.0, 398.0
19.0, 19.0

p34

p34

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e65 e23

e73

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c93 : 1
stoichiometry:c95 : 1
stoichiometry:c94 : 1

m65*m23*0.1

nodelay

--

true

0

false

PMID: 18086388 The cytoprotection was caused by the IFN-¦Ã-mediated induction of ER stress via activation of the pancreatic ER kinase (PERK).

Go back
798.0, 1642.0
19.0, 19.0

p35

p35

cso30:i:ME_Transcription

cso30:i:CC_Nucleolus

--

e66 e40

e70

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c91 : 1
stoichiometry:c92 : 1
stoichiometry:c90 : 1

m66*m40*0.1

nodelay

--

true

0

false

PMID: 18086388 in human endothelial cells IFN-¦Á can stimulate TTP transcription even without simultaneous p38 MAPK activation, suggesting that in these cells type I IFNs may directly elicit the TTP-dependent anti-inflammatory responses

Go back
705.0, 546.0
21.0, 21.0

p36

p36

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e75 e73

e74

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c96 : 1
stoichiometry:c98 : 1
stoichiometry:c97 : 1

m75*m73*0.1

nodelay

--

true

0

false

PMID: 18086388 ER stress and PERK activation result in phosphorylation of the ¦Á subunit of the eukaryotic translation initiation factor 2 (eIF2¦Á).

Go back
837.0, 697.0
21.0, 21.0

p37

p37

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e74

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c99 : 1

1.0*0.1

nodelay

--

true

0

false

PMID: 18086388 eIF2a phosphorylation imposes a strong reduction in translation that was previously associated with increased resistance to stress

Go back
1250.0, 521.5
20.5, 20.5

p4

p4

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e15 e17

e14

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c11 : 1
stoichiometry:c12 : 1

m15*m17*0.1

nodelay

--

true

0

false

PMID: 18086388, 8608598, 16571725, 8608597 Stat1 and Stat2 are essential for type I IFN responses whereas the still largely elusive role of Stat3 phosphorylation has only recently begun to emerge

Go back
1214.0, 770.0
19.0, 19.0

p5

p5

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

e14

e18

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c13 : 1
stoichiometry:c14 : 1

m14*0.1

nodelay

--

true

0

false

PMID: 18086388 After translocation to the nucleus Stat complexes bind to distinct enhancer elements and activate transcription of the type I IFN-responsive genes.

Go back
1023.0, 1211.0
17.0, 17.0

p6

p6

cso30:i:ME_Binding

cso30:i:CC_Nucleoplasm

--

e21 e18

e22

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c15 : 1
stoichiometry:c16 : 1
stoichiometry:c17 : 1

m21*m18*0.1

nodelay

--

true

0

false

PMID: 18086388 Herein, the ISGF3 complex consisting of a Stat1:Stat2 heterodimer and the DNA-binding subunit IRF9, which binds to ISRE elements, plays a more important role than the Stat1:Stat1 homodimer that binds to GAS elements.

Go back
878.0, 1298.0
19.0, 19.0

p7

p7

cso30:i:ME_DNABinding

cso30:i:CC_Nucleoplasm

--

e19 e22

e20

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c18 : 1
stoichiometry:c19 : 1
stoichiometry:c20 : 1

m19*m22*0.1

nodelay

--

true

0

false

PMID: 18086388 Herein, the ISGF3 complex consisting of a Stat1:Stat2 heterodimer and the DNA-binding subunit IRF9, which binds to ISRE elements, plays a more important role than the Stat1:Stat1 homodimer that binds to GAS elements.

Go back
961.0, 74.0
21.0, 21.0

p8

p8

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e24 e23 e25

e26

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c22 : 1
stoichiometry:c23 : 1
stoichiometry:c24 : 1

m24*m23*m25*0.1

nodelay

--

true

0

false

PMID: 18086388 Type II IFN signalling is initiated by binding of IFN-¦Ã to its receptor consisting of the IFNGR1 and IFNGR2 subunits.

Go back
1110.0, 82.0
19.0, 19.0

p9

p9

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e26

e27

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c25 : 1
stoichiometry:c26 : 1

m26*0.1

nodelay

--

true

0

false

PMID: 18086388 The receptor-associated Jak1 and Jak2 tyrosine kinases are activated and phosphorylate the receptor, thereby generating a docking site for the SH2 domain of Stat1.

Go back
1505.0, 244.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1279.0, 532.0

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1178.0, 532.0

c11

c11

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1260.0, 542.0

c12

c12

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1227.842250223113, 639.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1090.1697438559333, 789.0

c14

c14

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
958.0, 1204.0

c15

c15

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1044.4774036933125, 1233.830784576752

c16

c16

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1023.448073443305, 1228.0

c17

c17

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
888.0, 1242.0

c18

c18

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
904.7131906745911, 1275.0

c19

c19

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1508.0, 280.73544366254924

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
897.0, 1308.0

c20

c20

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
905.0, 100.79999546875531

c21

c21

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
989.30641508861, 47.0

c22

c22

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
973.8231932086841, 102.9575343506124

c23

c23

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
982.0, 94.0

c24

c24

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1076.0, 107.28590302650146

c25

c25

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1123.0, 101.0

c26

c26

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1158.0, 87.68695227583535

c27

c27

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1212.0, 81.0

c28

c28

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1256.0, 83.88741222571453

c29

c29

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1618.0, 276.0

c3

c3

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1172.0, 84.55738931387829

c30

c30

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1303.0, 77.0

c31

c31

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1344.0, 91.77829670735935

c32

c32

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1393.0, 85.0

c33

c33

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1395.028432229131, 183.0

c34

c34

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1362.8868084275553, 258.0

c35

c35

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1263.9424971120452, 174.97513947544527

c36

c36

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1360.0, 546.0

c37

c37

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1360.0, 650.0

c38

c38

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1337.9695445594657, 766.0

c39

c39

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1514.3148177390106, 284.0

c4

c4

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1173.2453897942512, 957.0

c40

c40

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1112.0241541460732, 1350.0

c41

c41

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1065.0, 1375.0

c42

c42

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1108.0, 1416.0

c43

c43

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
764.0, 1225.0

c44

c44

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
768.0954038833979, 184.0

c45

c45

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
717.6275411916054, 1339.0

c46

c46

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
711.0, 1392.0

c47

c47

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
679.0, 1343.0

c48

c48

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
724.0, 1588.0

c49

c49

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1508.0, 364.0

c5

c5

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
712.0, 1602.9999794544647

c50

c50

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
716.9570070272194, 184.0

c51

c51

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
960.0, 1394.0

c52

c52

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
976.0, 1512.0

c53

c53

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1293.0, 1512.0

c54

c54

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1061.0, 1560.0

c55

c55

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1058.9675801411856, 466.0

c56

c56

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1132.0, 1417.9216142504015

c57

c57

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
963.5623252907437, 916.0

c58

c58

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1061.0, 916.0

c59

c59

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1514.5458827133114, 419.0

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
234.0, 467.0

c60

c60

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
525.0, 710.6197177650145

c61

c61

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
704.0, 704.0

c62

c62

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
525.0, 828.0

c63

c63

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
709.0, 785.853612525057

c64

c64

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
336.0, 781.0

c65

c65

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1066.6964523622858, 923.094803727613

c66

c66

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1320.4773840485057, 466.0

c67

c67

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
681.0, 1333.0

c68

c68

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
859.7825984120171, 1457.0

c69

c69

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1187.0, 448.0

c7

c7

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
830.0, 802.0

c70

c70

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
560.6434365067173, 1661.4569890488103

c71

c71

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
548.0, 1513.0

c72

c72

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
556.1319453618936, 1665.8503304684027

c73

c73

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
564.0, 1492.0

c74

c74

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1153.2065767803003, 1425.0

c75

c75

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1121.9895013078128, 1337.0

c76

c76

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1020.0, 1340.0

c77

c77

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1012.4198060380144, 1421.8843608412726

c78

c78

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
957.9909451017955, 1408.0

c79

c79

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1338.0, 456.0

c8

c8

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1000.0, 1354.0

c80

c80

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
773.0, 981.0

c81

c81

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
913.490304619763, 1421.0

c82

c82

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
912.0, 1552.0

c83

c83

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1242.0, 1655.0

c84

c84

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
931.0, 1655.0272107269502

c85

c85

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
888.6210148120329, 1453.6994857254588

c86

c86

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
691.1119090269775, 1061.9223518172148

c87

c87

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
707.8320415642386, 1143.4819476460627

c88

c88

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
715.0363082783794, 1136.604003079615

c89

c89

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1352.0, 448.0

c9

c9

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
817.0, 1652.0

c90

c90

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
823.2524175123802, 1467.0

c91

c91

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
717.0, 1668.5461490414018

c92

c92

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
870.0, 351.0

c93

c93

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
872.0, 417.0

c94

c94

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
880.8265607392966, 51.0

c95

c95

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
700.0, 486.0

c96

c96

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
726.0, 565.0

c97

c97

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
733.3174928327581, 496.0

c98

c98

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
822.0, 648.0

c99

c99

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back